Skip to main content
SpringerLink
Log in

Natural Anticancer Compounds and Their Derivatives in Clinical Trials

  • Chapter
  • First Online:
Book cover Anticancer Plants: Clinical Trials and Nanotechnology

Abstract

Cancer continues to be a global challenge to both clinicians and researchers with an increasing mortality rate. Despite the enormous progress made in the anticancer drug discovery, there is a constant demand for novel therapeutic agents, because of the development of resistance to the existing chemotherapeutic drugs and their adverse side effects. The anticancer drugs derived from the natural sources have shown to be effective and safe in the treatment of cancers. Secondary metabolite compounds from plants such as alkaloids, flavonoids, and carotenoids are known for their cancer prevention and antitumor properties. Peptides produced from marine organisms and anthracyclines synthesized by microbes as secondary metabolites are also known for their anticancer properties. Some of these natural compounds are widely used in cancer therapy, and some are under clinical or preclinical trials. Some of the potential anticancer agents from plants (paclitaxel, vincristine, vinblastine, irinotecan, etoposide, topotecan, and camptothecin), marines (dolastatin 10, cytarabine, and aplidine), and microorganisms (bleomycin, doxorubicin, and dactinomycin) have been used in cancer therapy. Cancers are characterized by the alterations in the cell signaling pathways. Most of the current anticancer therapies involve the modulation of altered signaling targets in cancers. The advantage of using natural compounds with antitumor properties for cancer therapy is that the compounds have well-defined signaling targets with a minimal toxicity. Natural anticancer drugs have been categorized based on their target-specific signaling pathways, which include DNA-damaging drugs, methyltransferase inhibitors, mitotic disrupters, and histone deacetylase inhibitors. Thus, the present chapter highlights the natural anticancer compounds and their derivatives which are under clinical trials and their mechanism of action in cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anitha Sri S (2016) Pharmacological activity of vinca alkaloids. J Pharmacogn Phytochem 4:27–34

    Google Scholar 

  • Arastu-Kapur S, Anderl JL, Kraus M, Parlati F, Shenk KD, Lee SJ, Muchamuel T, Bennett MK, Driessen C, Ball AJ, Kirk CJ (2011) Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res 17:2734–2743

    Article  PubMed  CAS  Google Scholar 

  • Arora S, Gonzalez AF, Solanki K (2013) Combretastatin A-4 and its analogs in cancer therapy. Int J Pharm Sci Rev Res 22:168–174

    Google Scholar 

  • Badgujar VB, Ansari MT, Abdullah MS (2015) Homoharringtonine: a nascent phytochemical for cancer treatment. World J Pharm Pharm Sci 4:1380–1391

    CAS  Google Scholar 

  • Baghel SS, Shrivastava N, Baghel RS (2016) A review of quercetin: antioxidant and anticancer properties. World J Pharm Pharm Sci 1:146–160

    Google Scholar 

  • Ballou LM, Lin RZ (2008) Rapamycin and mTOR kinase inhibitors. J Chem Biol 1:27–36

    Article  PubMed  PubMed Central  Google Scholar 

  • Bayala B, Bassole IH, Scifo R, Gnoula C, Morel L, Lobaccaro JMA, Simpore J (2014) Anticancer activity of essential oils and their chemical components-a review. Am J Cancer Res 4:591–607

    PubMed  PubMed Central  CAS  Google Scholar 

  • Behrangi N, Hashemi M, Borna H (2012) Microtubules and tubulins as target for some natural anticancer agents extracted from marines, bacteruim, and fungus. Adv Stud Biol 4:1–9

    Google Scholar 

  • Bennouna J, Delord JP, Campone M, Nguyen L (2008) Vinflunine: a new microtubule inhibitor agent. Clin Cancer Res 14:1625–1632

    Article  PubMed  CAS  Google Scholar 

  • Bhanot A, Sharma R, Noolvi MN, Bhanot SR, Noolvi MN (2011) Natural sources as potential anticancer agents: a review. Int J Phytomed 3:9–26

    Google Scholar 

  • Bhatnagar I, Kim SK (2010) Marine antitumor drugs: status, shortfalls and strategies. Mar Drugs 8:2702–2720

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bhattacharya B, Mukherjee S (2015) Cancer therapy using antibiotics. J Cancer Ther 6:849–858

    Article  CAS  Google Scholar 

  • Bhuvaneswari V, Nagini S (2005) Lycopene: a review of its potential as an anticancer agent. Curr Med Chem 5:627–635

    CAS  Google Scholar 

  • Biggar RJ, Wohlfahrt J, Melbye M (2012) Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix. Int J Cancer 131:716–721

    Article  PubMed  CAS  Google Scholar 

  • Biggar RJ, Andersen EW, Kroman N, Wohlfahrt J, Melbye M (2013) Breast cancer in women using digoxin: tumor characteristics and relapse risk. Breast Cancer Res 15:R13. https://doi.org/10.1186/bcr3386

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blasiak J, Sikora A, Wozniak K, Drzewoski J (2004) Genotoxicity of streptozotocin in normal and cancer cells and its modulation by free radical scavengers. Cell Biol Toxicol 20:83–96

    Article  PubMed  CAS  Google Scholar 

  • Brunello A, Roma A, Basso U, Jirillo A (2010) A review of Vinorelbine in the treatment of advanced breast cancer. Clin Med Ther 1:1715–1726

    Google Scholar 

  • Butler MS, Robertson AAB, Cooper MA (2014) Natural product and natural product derived drugs in clinical trials. Nat Prod Rep 31:1612–1661

    Article  PubMed  CAS  Google Scholar 

  • Calderón-Montaño JM, Burgos-Morón E, Orta ML, Maldonado-Navas D, García-Domínguez I, López-Lázaro M (2014) Evaluating the cancer therapeutic potential of cardiac glycosides. Biomed Res Int 2014:794930. https://doi.org/10.1155/2014/794930

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao W, Liu Y, Zhang R, Zhang B, Wang T, Zhu X, Mei L, Chen H, Zhang H, Ming P, Huang L (2015) Homoharringtonine induces apoptosis and inhibits STAT3 via IL-6/JAK1/STAT3 signal pathway in Gefitinib-resistant lung cancer cells. Sci Rep 5:8477. https://doi.org/10.1038/srep08477

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen J, Song Y, Zhang L (2013) Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies. J Nutr Sci Vitaminol 59:213–223

    Article  PubMed  CAS  Google Scholar 

  • Cheung-Ong K, Giaever G, Nislow C (2013) DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem Biol 20:648–659

    Article  PubMed  CAS  Google Scholar 

  • Chinta G, Syed SB, MSC C, Periyasamy L (2015) Piperine: a comprehensive review of pre-clinical and clinical investigations. Curr Bioact Compd 11:156–169

    Article  CAS  Google Scholar 

  • Choi JY, Hong WG, Cho JH, Kim EM, Kim J, Jung CH, Hwang SG, Um HD, Park JK (2015) Podophyllotoxin acetate triggers anticancer effects against non-small cell lung cancer cells by promoting cell death via cell cycle arrest, ER stress and autophagy. Int J Oncol 47:1257–1265

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chung KS, Yim N-H, Lee SH, Choi SJ, Hur KS, Hoe KL, Kim DU, Goehle S, Kim HB, Song KB, Yoo HS, Bae KH, Simon J, Won M (2008) Identification of small molecules inducing apoptosis by cell-based assay using fission yeast deletion mutants. Investig New Drugs 26:299–307

    Article  CAS  Google Scholar 

  • Cragg GM, Newman DJ (2005) Plants as a source of anti-cancer agents. J Ethnopharmacol 100:72–79

    Article  CAS  PubMed  Google Scholar 

  • Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830:3670–3695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cragg GM, Grothaus PG, Newman DJ (2009) Impact of natural products on developing new anti-cancer agents. Chem Rev 109:3012–3043

    Article  PubMed  CAS  Google Scholar 

  • Crawford LJ, Walker B, Irvine AE (2011) Proteasome inhibitors in cancer therapy. J Cell Commun Signal 5:101–110

    Article  PubMed  PubMed Central  Google Scholar 

  • Cushnie TPT, Cushnie B, Lamb AJ (2014) Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int J Antimicrob Agents 44:377–386

    Article  PubMed  CAS  Google Scholar 

  • D’Incalci M, Galmarini CM (2010) A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 9:2157–2163

    Article  PubMed  CAS  Google Scholar 

  • Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Damelin M, Bankovich A, Park A, Aguilar J, Anderson W, Santaguida M, Aujay M, Fong S, Khandke K, Pulito V, Ernstoff E, Escarpe P, Bernstein J, Pysz M, Zhong W, Upeslacis E, Lucas JJ, Lucas JJ, Nichols T, Loving K, Foord O, Hampl J, Stull R, Barletta F, Falahatpisheh H, Sapra P, Gerber HP, Dylla SJ (2015) Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clin Cancer Res 21:4165–4173

    Article  PubMed  CAS  Google Scholar 

  • Del Rio D, Stalmach A, Calani L, Crozier A (2010) Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols. Forum Nutr 2:820–833

    Google Scholar 

  • Demain AL, Vaishnav P (2011) Natural products for cancer chemotherapy. Microb Biotechnol 4:687–699

    Article  PubMed  PubMed Central  Google Scholar 

  • Dixit RB, Suseela MR (2013) Cyanobacteria: potential candidates for drug discovery. Antonie Van Leeuwenhoek 103:947–961

    Article  PubMed  CAS  Google Scholar 

  • Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, Hunger S, Krishnamurthi SS, Lassman AB, Markham MJ, Mayer E, Neuss M, Pal SK, Richardson LC, Schilsky R, Schwartz GK, Spriggs DR, Villalona-Calero MA, Villani G, Masters G (2016) Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol 34:987–1011

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Fu YJ, Zu YG, Schwarz G, Konkimalla VSB, Wink M (2007) Molecular target-guided tumor therapy with natural products derived from traditional Chinese medicine. Curr Med Chem 14:2024–2032

    Article  PubMed  CAS  Google Scholar 

  • Escuin D, Kline ER, Giannakakou P (2005) Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1. Accumulation and activity by disrupting microtubule function. Cancer Res 65:9021–9028

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Fanale D, Bronte G, Passiglia F, Calo V, Castiglia M, Di Piazza F, Barraco N, Cangemi A, Catarella MT, Insalaco L, Listi A, Maragliano R, Massihnia D, Perez A, Toia F, Cicero G, Bazan V (2015) Stabilizing versus destabilizing the microtubules: a double-edge sword for an effective cancer treatment option. Anal Cell Pathol 2015:690916. https://doi.org/10.1155/2015/690916

    Article  CAS  Google Scholar 

  • Fauzee NJS, Dong Z, Wang YL (2011) Taxanes: promising anti-cancer drugs. Asian Pac J Cancer Prev 12:837–851

    PubMed  Google Scholar 

  • Ferrandina G, Mariani M, Andreoli M, Shahabi S, Scambia G, Ferlini C (2012) Novel drugs targeting microtubules: the role of epothilones. Curr Pharm Des 18:2793–2803

    Article  PubMed  CAS  Google Scholar 

  • Florento L, Matias R, Tuaño E, Santiago K, Dela Cruz F, Tuazon A (2012) Comparison of cytotoxic activity of anticancer drugs against various human tumor cell lines using in vitro cell-based approach. Int J Biomed Sci 8:76–80

    Google Scholar 

  • Foss F, Horwitz S, Pro B, Prince HM, Sokol L, Balser B, Wolfson J, Coiffier B (2016) Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial. J Hematol Oncol 9:22. https://doi.org/10.1186/s13045-016-0243-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fukuyo Y, Hunt CR, Horikoshi N (2010) Geldanamycin and its anti-cancer activities. Cancer Lett 290:24–35

    Article  PubMed  CAS  Google Scholar 

  • Ganguly A, Yang H, Cabral F (2010) Paclitaxel-dependent cell lines reveal a novel drug activity. Mol Cancer Ther 9:2914–2923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gibellini L, Pinti M, Nasi M, Montagna JP, De Biasi S, Roat E, Bertoncelli L, Cooper EL, Cossarizza A (2011) Quercetin and cancer chemoprevention. Evid Based Compl Altern Med 2011:591356. https://doi.org/10.1093/ecam/neq053

    Article  Google Scholar 

  • Giddings LA, Newman DJ (2013) Microbial natural products: molecular blueprints for antitumor drugs. J Ind Microbiol Biotechnol 40:1181–1210

    Article  PubMed  CAS  Google Scholar 

  • Gomes NGM, Lefranc F, Kijjoa A, Kiss R (2015) Can some marine-derived fungal metabolites become actual anticancer agents. Mar Drugs 13:3950–3991

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gordaliza M, Castro MA, del Corral JM, Feliciano AS (2000) Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des 6:1811–1839

    Article  PubMed  CAS  Google Scholar 

  • Greenwell M, Rahman PKSM (2015) Medicinal plants: their use in anticancer treatment. Int J Pharm Sci Res 6:4103–4112

    PubMed  PubMed Central  CAS  Google Scholar 

  • Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13:894–901

    Article  PubMed  CAS  Google Scholar 

  • Hecht SM (2000) Bleomycin: new perspectives on the mechanism of action. J Nat Prod 63:158–168

    Article  PubMed  CAS  Google Scholar 

  • Hoelder S, Clarke PA, Workman P (2012) Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol 6:155–176

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang M, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT (2012) Terpenoids: natural products for cancer therapy. Expert Opin Investig Drugs 21:1801–1818

    Article  PubMed  CAS  Google Scholar 

  • Hussain MS, Fareed S, Ansari S, Khan MS (2012) Marine natural products: a lead for anti-cancer. Indian J Mar Sci 41:891–903

    Google Scholar 

  • Imperatore C, Aiello A, D’Aniello F, Senese M, Menna M (2014) Alkaloids from marine invertebrates as important leads for anticancer drugs discovery and development. Molecules 19:20391–20423

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Irie K, Yanagita RC, Nakagawa Y (2012) Challenges to the development of bryostatin-type anticancer drugs based on the activation mechanism of protein kinase Cδ. Med Res Rev 32:518–535

    Article  PubMed  CAS  Google Scholar 

  • Jimeno J, Faircloth G, Sousa-Faro JF, Scheuer P, Rinehart K (2004) New marine derived anticancer therapeutics – a journey from the sea to clinical trials. Mar Drugs 2:14–29

    Article  PubMed Central  CAS  Google Scholar 

  • Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265

    Article  PubMed  CAS  Google Scholar 

  • Jordan M, Toso RJ, Thrower D, Wilson L (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci U S A 90:9552–9556

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kathiravan MK, Khilare MM, Nikoomanesh K, Chothe AS, Jain KS (2013) Topoisomerase as target for antibacterial and anticancer drug discovery. J Enzyme Inhib Med Chem 28:419–435

    Article  PubMed  CAS  Google Scholar 

  • Kaur R, Arora S (2015) Alkaloids-important therapeutic secondary metabolites of plant origin. J Crit Rev 2:1–8

    Google Scholar 

  • Kepp O, Menger L, Vacchelli E, Adjemian S, Martins I, Ma Y, Sukkurwala AQ, Michaud M, Galluzzi L, Zitvogel L, Kroemer G (2012) Anticancer activity of cardiac glycosides: at the frontier between cell-autonomous and immunological effects. Oncoimmunology 1:1640–1642

    Article  PubMed  PubMed Central  Google Scholar 

  • Khazir J, Riley DL, Pilcher LA, De-Maayer P, Mir BA (2014) Anticancer agents from diverse natural sources. Nat Prod Commun 9:1655–1669

    PubMed  Google Scholar 

  • Kinghorn AD (2015) Review of anticancer agents from natural products. J Nat Prod 78:2315–2315

    Article  CAS  Google Scholar 

  • Kinghorn AD, Carcache De Blanco EJ, Lucas DM, Rakotondraibe HL, Orjala J, Soejarto DD, Oberlies NH, Pearce CJ, Wani MC, Stockwell BR, Burdette JE, Swanson SM, Fuchs JR, Phelps MA, Xu L, Zhang X, Shen YY (2016) Discovery of anticancer agents of diverse natural origin. Anticancer Res 36:5623–5637

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kumar S (2015) Drug targets for cancer treatment: an overview. Med Chem 5:115–123

    Article  CAS  Google Scholar 

  • Kuznetsov G, TenDyke K, Towle MJ, Cheng H, Liu J, Marsh JP, Schiller SER, Spyvee MR, Yang H, Seletsky BM, Shaffer CJ, Marceau V, Yao Y, Suh EM, Campagna S, Fang FG, Kowalczyk JJ, Littlefield BA (2009) Tubulin-based antimitotic mechanism of E7974, a novel analogue of the marine sponge natural product hemiasterlin. Mol Cancer Ther 8:2852–2860

    Article  PubMed  CAS  Google Scholar 

  • Lee W, St.Onge RP, Proctor M, Flaherty P, Jordan MI, Arkin AP, Davis RW, Nislow C, Giaever G (2005) Genome-wide requirements for resistance to functionally distinct DNA-damaging agents. PLoS Genet 1:e24. https://doi.org/10.1371/journal.pgen.0010024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK (2006) Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites. Mol Cancer Ther 5:2737–2746

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Zhang T, Schwartz SJ, Sun D (2009) New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential. Drug Resist Updat 12:17–27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li J, Kim SG, Blenis J (2014a) Rapamycin: one drug, many effects. Cell Metab 19:373–379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Y, Lu X, Qi H, Li X, Xiao X, Gao J (2014b) Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and suppression of ERK1/2 MAPK in HeLa cells. J Pharmacol Sci 125:202–210

    Article  PubMed  CAS  Google Scholar 

  • Li K, Chung-Davidson YW, Bussy U, Li W (2015) Recent advances and applications of experimental technologies in marine natural product research. Mar Drugs 13:2694–2713

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lin RK, Hsu CH, Wang YC (2007) Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells. Anti-Cancer Drugs 18:1157–1164

    Article  PubMed  CAS  Google Scholar 

  • Lippi G, Targher G (2011) Tomatoes, lycopene-containing foods and cancer risk. Br J Cancer 104:1234–1235

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lo YS, Tseng WH, Chuang CY, Hou MH (2013) The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats. Nucleic Acids Res 41:4284–4294

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lopez-Lazaro M (2009) Digoxin, HIF-1, and cancer. Proc Natl Acad Sci U S A 106:E26–E27

    Article  PubMed  PubMed Central  Google Scholar 

  • Lü S, Wang J (2014) Homoharringtonine and omacetaxine for myeloid hematological malignancies. J Hematol Oncol 7:2. https://doi.org/10.1186/1756-8722-7-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu JJ, Bao JL, Chen XP, Huang M, Wang YT (2012) Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Compl Altern Med 2012:485042. https://doi.org/10.1155/2012/485042

    Article  Google Scholar 

  • Luthria DL, Mukhopadhyay S (2006) Influence of sample preparation on assay of phenolic acids from eggplant. J Agric Food Chem 54:41–47

    Article  PubMed  CAS  Google Scholar 

  • Mans DRA (2016) Exploring the global animal biodiversity in the search for new drugs-marine invertebrates exploring the global animal biodiversity in the search for new drugs – marine invertebrates. J Transl Sci 2:170–179

    Google Scholar 

  • Mariaule G, Belmont P (2014) Cyclin-dependent kinase inhibitors as marketed anticancer drugs: where are we now. A short survey. Molecules 19:14366–14382

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Martin DM (2003) Induction of volatile terpene biosynthesis and diurnal emission by methyl jasmonate in foliage of Norway spruce. Plant Physiol 132:1586–1599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mastron JK, Siveen KS, Sethi G, Bishayee A (2015) Silymarin and hepatocellular carcinoma: a systematic, comprehensive, and critical review. Anti-Cancer Drugs 26:475–486

    Article  PubMed  CAS  Google Scholar 

  • McKinney JS, Sethi S, Tripp JD, Nguyen TN, Sanderson BA, Westmoreland JW, Resnick MA, Lewis LK (2013) A multistep genomic screen identifies new genes required for repair of DNA double-strand breaks in Saccharomyces cerevisiae. BMC Genomics 14:251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mehta HJ, Patel V, Sadikot RT (2014) Curcumin and lung cancer-a review. Target Oncol 9:295–310

    Article  PubMed  Google Scholar 

  • Melorose J, Perroy R, Careas S, Martin LP, Hamilton TC, Schilder RJ, Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 14:1291–1295

    Google Scholar 

  • Miura S, Izuta S (2004) DNA polymerases as targets of anticancer nucleosides. Curr Drug Targets 5:191–195

    Article  PubMed  CAS  Google Scholar 

  • Moore BS, Eustáquio AS, McGlinchey RP (2008) Advances in and applications of proteasome inhibitors. Curr Opin Chem Biol 12:434–440

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mottamal M, Zheng S, Huang T, Wang G (2015) Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 20:3898–3941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moudi M, Go R, Yien CYS, Nazre M (2013) Vinca alkaloids. Int J Prev Med 4:1131–1135

    Google Scholar 

  • Mukhtar E, Adhami VM, Mukhtar H (2014) Targeting microtubules by natural agents for cancer therapy. Mol Cancer Ther 13:275–284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Munoz-Alonso M, Gonza L, Zarich N, Martı T, Alvarez E (2008) Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via Rac1/c-Jun NH2-terminal kinase activation in human melanoma cells. J Pharmacol Exp Ther 324:1093–1101

    Article  PubMed  CAS  Google Scholar 

  • Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:55–61

    Article  Google Scholar 

  • Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2014) Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development. Mar Drugs 12:255–278

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2016a) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79:629–661

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2016b) Drugs and drug candidates from marine sources: an assessment of the current “State of play”. Planta Med 82:775–789

    Article  PubMed  CAS  Google Scholar 

  • Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037

    Article  CAS  PubMed  Google Scholar 

  • Nicolaou KC, Smitht AL, Yue EW (1993) Review chemistry and biology of natural and designed enediynes. Proc Natl Acad Sci 90:5881–5888

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nijwening JH, Kuiken HJ, Beijersbergen RL (2011) Screening for modulators of cisplatin sensitivity: unbiased screens reveal common themes. Cell Cycle 10:380–386

    Article  PubMed  CAS  Google Scholar 

  • Orlowski RZ, Kuhn DJ (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res 14:1649–1657

    Article  PubMed  CAS  Google Scholar 

  • Ozcan T, Akpinar-Bayizit A, Yilmaz-Ersan L, Delikanli B (2014) Phenolics in human health. Int J Chem Eng Appl 5:393–396

    CAS  Google Scholar 

  • Pangestuti R, Kim SK (2017) Bioactive peptide of marine origin for the prevention and treatment of non-communicable diseases. Mar Drugs 15:1–23

    Article  CAS  Google Scholar 

  • Pavese JM, Farmer RL, Bergan RC (2010) Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev 29:465–482

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Petek BJ, Jones RL (2014) PM00104 (Zalypsis®): a marine derived alkylating agent. Molecules 19:12328–12335

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Pichersky E (2006) Biosynthesis of plant volatiles: nature’s diversity and ingenuity. Science 311:808–811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pommier Y (2006) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6:789–802

    Article  PubMed  CAS  Google Scholar 

  • Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S, Guha S, Aggarwal BB (2012) Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res 18:4942–4953

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Priyadarshini K, Keerthi A (2012) Paclitaxel against cancer: a short review. Med Chem 2:142–146

    Google Scholar 

  • Priyankashukla XX (2014) Marine natural products as anticancer agents. J Pharm Biol Sci 9:60–64

    Google Scholar 

  • Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the united states. Cancer Res 74:2913–2921

    Article  PubMed  CAS  Google Scholar 

  • Rahmani AH, Al Zohairy MA, Aly SM, Khan MA (2014) Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int 2014:761608. https://doi.org/10.1155/2014/761608

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Raju U, Nakata E, Mason KA, Ang KK, Milas L (2003) Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells. Cancer Res 63:3263–3267

    PubMed  CAS  Google Scholar 

  • Ramasamy K, Agarwal R (2008) Multitargeted therapy of cancer by silymarin. Cancer Lett 269:352–362

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rangel M, Falkenberg M (2015) An overview of the marine natural products in clinical trials and on the market. J Coast Life Med 3:421–428

    CAS  Google Scholar 

  • Ray A, Okouneva T, Manna T, Miller HP, Schmid S, Arthaud L, Luduena R, Jordan MA, Wilson L (2007) Mechanism of action of the microtubule-targeted antimitotic depsipeptide tasidotin (formerly ILX651) and its major metabolite tasidotin C-carboxylate. Cancer Res 67:3767–3776

    Article  PubMed  CAS  Google Scholar 

  • Raza A, Aslam B, Naseer MU, Ali A, Majeed W, Hassan SU (2015) Antitumor activity of berberine against breast cancer: a review. Int Res J Pharm 6:81–85

    Article  CAS  Google Scholar 

  • Reichenbach H, Höfle G (2008) Discovery and development of the epothilones: a novel class of antineoplastic drugs. Drugs R D 9:1–10

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Reusser F (1971) Mode of action of streptozotocin. J Bacteriol 105:580–588

    PubMed  PubMed Central  CAS  Google Scholar 

  • Rida PCG, Livecche D, Ogden A, Zhou J, Aneja R (2015) The noscapine chronicle: a pharmaco-historic biography of the opiate alkaloid family and its clinical applications. Med Res Rev 35:1072–1096

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Robert J (2007) Preclinical assessment of anthracycline cardiotoxicity in laboratory animals: predictiveness and pitfalls. Cell Biol Toxicol 23:27–37

    Article  PubMed  CAS  Google Scholar 

  • Rocha LD, Monteiro MC, Teodoro AJ (2012) Anticancer properties of hydroxycinnamic acids-a review. Cancer Clin Oncol 1:109–121

    Google Scholar 

  • Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, García-Fernández LF, Cuevas C, Allavena P, Erba E, D’Incalci M (2013) Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104). Int J Cancer 133:2024–2033

    Article  PubMed  CAS  Google Scholar 

  • Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, Nabavi SM (2016) Understanding genistein in cancer: the “good” and the “bad” effects: a review. Food Chem 196:589–600

    Article  PubMed  CAS  Google Scholar 

  • Salem M, Rohani S, Gillies ER (2014) Curcumin, a promising anti-cancer therapeutic: a review of its chemical properties, bioactivity and approaches to cancer cell delivery. RSC Adv 4:10815

    Article  CAS  Google Scholar 

  • Schutz FA, Bellmunt J, Rosenberg JE, Choueiri TK (2011) Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid. Expert Opin Drug Saf 10:645–653

    Article  PubMed  CAS  Google Scholar 

  • Schwartsmann G, da Rocha AB, Berlinck RG, Jimeno J (2001) Marine organisms as a source of new anticancer agents. Lancet Oncol 2:221–225

    Article  PubMed  CAS  Google Scholar 

  • Scully OJ, Bay BH, Yip G, Yu Y (2012) Breast cancer metastasis. Cancer Genomics Proteomics 9:311–320

    PubMed  CAS  Google Scholar 

  • Seto B (2012) Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med 1:29. https://doi.org/10.1186/2001-1326-1-29

    Article  PubMed  PubMed Central  Google Scholar 

  • Shan J, Xuan Y, Ruan S, Sun M (2011) Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med 17:607–611

    Article  PubMed  CAS  Google Scholar 

  • Shapiro RS (2015) Antimicrobial induced DNA damage and genomic instability in microbial pathogens. PLoS Pathog 11:e1004678. https://doi.org/10.1371/journal.ppat.1004678

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shen B, Hindra YX, Huang T, Ge H, Yang D, Teng Q, Rudolf JD, Lohman JR (2015) Enediynes: exploration of microbial genomics to discover new anticancer drug leads. Bioorg Med Chem Lett 25:9–15

    Article  PubMed  CAS  Google Scholar 

  • Siegel RL, Miller KDJA (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30

    Article  PubMed  Google Scholar 

  • Siemann DW, Chaplin DJ, Walicke PA (2009) A review and update of the current status of the vasculature-disabling agent combretastatin-A4 phosphate (CA4P). Expert Opin Investig Drugs 18:189–197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Simmons TL, Andrianasolo E, Mcphail K, Flatt P, Gerwick WH (2005) Minireview marine natural products as anticancer drugs. Mol Cancer Ther 4:333–342

    PubMed  CAS  Google Scholar 

  • Simon J, Szankasi P, Nguyen DK, Ludlow C, Dunstan HM, Roberts CJ, Jensen EL, Hartwell LH, Friend SH (2000) Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae 1. Cancer Res 60:328–333

    PubMed  CAS  Google Scholar 

  • Singh A, Duggal S (2009) Piperine-review of advances in pharmacology. Int J Pharm Sci Nanotechnol 2:615–620

    CAS  Google Scholar 

  • Singh B, Sharma RA (2015) Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech 5:129–151

    Article  PubMed  Google Scholar 

  • Singh R, Sharma M, Joshi P, Rawat DS (2008) Clinical status of anti-cancer agents derived from marine sources. Anti Cancer Agents Med Chem 8:603–617

    Article  CAS  Google Scholar 

  • Sobral MV, Xavier AL, Lima TC, De Sousa DP (2014) Antitumor activity of monoterpenes found in essential oils. Sci World J 2014:953451. https://doi.org/10.1155/2014/953451

    Article  CAS  Google Scholar 

  • Souto AL, Tavares JF, Da Silva MS, De Diniz MFFM, De Athayde-Filho PF, Barbosa Filho JM (2011) Anti-inflammatory activity of alkaloids: an update from 2000 to 2010. Molecules 16:8515–8534

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Spagnuolu C, Russo GL, Orhan Llkay E, Habtemariam S, Daglia M, Sureda A, Nabavi SF, Devi KP, Loizzo MR, Tundis R, Nabavi SM (2015) Genistein and cancer: current status, challenges, and future directions. Adv Nutr An Int Rev J 6:408–419

    Article  CAS  Google Scholar 

  • Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Choudhary B, Raghavan SC (2016) Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep 6:24049. https://doi.org/10.1038/srep24049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stanton RA, Gernert KM, Nettles JH, Aneja R (2011) Drugs that target dynamic microtubules: a new molecular perspective. Med Res Rev 31:443–481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun J (2007) D-limonene: safety and clinical applications. Altern Med Rev 12:259–264

    PubMed  Google Scholar 

  • Sun Y, Xun K, Wang Y, Chen X (2009) A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Anti-Cancer Drugs 20:757–769

    Article  PubMed  CAS  Google Scholar 

  • Takebayashi Y, Pourquier P, Zimonjic DB, Nakayama K, Emmert S, Ueda T, Urasaki Y, Kanzaki A, Akiyama S, Popescu N, Kraemer KH, Pommier Y (2001) Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide excision repair. Nat Med 7:961–966

    Article  PubMed  CAS  Google Scholar 

  • Tan AR, Swain SM (2002) Review of flavopiridol, a cyclin-dependent kinase inhibitor, as breast cancer therapy. Semin Oncol 29:77–85

    Article  PubMed  CAS  Google Scholar 

  • Thakur NL, Thakur AN, Müller WEG (2005) Marine natural products in drug discovery. Nat Prod Radiance 4:471–477

    Google Scholar 

  • Tiong SH, Looi CY, Hazni H, Arya A, Paydar M, Wong WF, Cheah SC, Mustafa MR, Awang K (2013) Antidiabetic and antioxidant properties of alkaloids from Catharanthus roseus (L.) G. Don. Molecules 18:9770–9784

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tomasz M (1995) Mitomycin C: small, fast and deadly (but very selective). Chem Biol 2:575–579

    Article  PubMed  CAS  Google Scholar 

  • Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA (2001) In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res 61:1013–1021

    Google Scholar 

  • Tu HY, Huang AM, Wei BL, Gan KH, Hour TC, Yang SC, Pu YS, Lin CN (2009) Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg Med Chem 17:7265–7274

    Article  PubMed  CAS  Google Scholar 

  • Vasavirama K, Upender M (2014) Piperine: a valuable alkaloid from piper species. Int J Pharm Pharm Sci 6:34–38

    Google Scholar 

  • Venditto VJ, Simanek EE (2010) Cancer therapies utilizing the camptothecins: a review of the in vivo literature. Mol Pharm 7:307–349

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wahid M, Bano Q (2014) Structure activity relationship and clinical development perspective of analogs. J Appl Pharmacol 6:286–295

    CAS  Google Scholar 

  • Waksman SA, Woodruff HB (1941) Actinomyces antibioticus, a new soil organism antagonistic to pathogenic and non-pathogenic bacteria 1. J Bacteriol 42:231–249

    PubMed  PubMed Central  CAS  Google Scholar 

  • Wang J, Ren T, Xi T (2012) Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7 human breast cancer cells. Med Oncol 29:10–15

    Article  PubMed  CAS  Google Scholar 

  • Wang XH, Zhou SY, Qian ZZ, Zhang HL, Qiu LH, Song Z, Zhao J, Wang P, Hao XS, Wang HQ (2013) Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors. Expert Opin Drug Metab Toxicol 9:117–125

    Article  PubMed  CAS  Google Scholar 

  • Wei MY, Giovannucci EL (2012) Lycopene, tomato products, and prostate cancer incidence: a review and reassessment in the PSA screening era. J Oncol 2012:271063. https://doi.org/10.1155/2012/271063

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wellington KW (2015) Understanding cancer and the anticancer activities of naphthoquinones – a review. RSC Adv 5:20309–20338

    Article  CAS  Google Scholar 

  • Wilken R, Veena MS, Wang MB, Srivatsan ES (2011) Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 10:12. https://doi.org/10.1186/1476-4598-10-12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wondrak GT (2009) Redox-directed cancer therapeutics: molecular mechanisms and opportunities. Antioxid Redox Signal 11:3013–3069

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wozniak L, Skapska S, Marszalek K (2015) Ursolic acid – a pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules 20:20614–20641

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Xu WS, Parmigiani RB, Marks PA (2007) Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26:5541–5552

    Article  PubMed  CAS  Google Scholar 

  • Yan Z, Zhu Z, Qian Z, Zhao C, Wang H, Ying G (2013) A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors. Int J Nanomedicine 8:129–136

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhen J, Villani TS, Guo Y, Qi Y, Chin K, Pan MH, Ho CT, Simon JE, Wu Q (2016) Phytochemistry, antioxidant capacity, total phenolic content and anti-inflammatory activity of Hibiscus sabdariffa leaves. Food Chem 190:673–680

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Giannakakou P (2005) Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents 5:65–71

    Article  PubMed  CAS  Google Scholar 

  • Ziegler J, Facchini PJ (2008) Alkaloid biosynthesis: metabolism and trafficking. Annu Rev Plant Biol 59:735–769

    Article  PubMed  CAS  Google Scholar 

  • Zwergel C, Valente S, Mai A (2015) DNA methyltransferases inhibitors from natural sources. Curr Top Med Chem 16:680–696

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, India

    Veerabhadrappa Bhavana, Setra Janardhana Shetty Sudharshan & Dyavaiah Madhu

  2. DBT-IPLS Program, School of Life Sciences, Pondicherry University, Pondicherry, India

    Setra Janardhana Shetty Sudharshan & Dyavaiah Madhu

Authors
  1. Veerabhadrappa Bhavana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Setra Janardhana Shetty Sudharshan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dyavaiah Madhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Botany, Gandhi Faiz-e-Aam College, Shahjahanpur, Uttar Pradesh, India

    Mohd Sayeed Akhtar

  2. Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

    Mallappa Kumara Swamy

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bhavana, V., Sudharshan, S.J.S., Madhu, D. (2017). Natural Anticancer Compounds and Their Derivatives in Clinical Trials. In: Akhtar, M., Swamy, M. (eds) Anticancer Plants: Clinical Trials and Nanotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-10-8216-0_3

Download citation

Publish with us

Policies and ethics

Search

Navigation